ABSTRACT
BACKGROUND: Ionizing radiation plays a significant role in cancer treatment. Despite recent advances in radiotherapy approaches, the existence of irradiation-resistant cancer cells is still a noteworthy challenge. Therefore, developing novel therapeutic approaches are still warranted in order to increase the sensitivity of tumor cells to radiation. Many types of research rely on the role of mitochondria in radiation protection. OBJECTIVE: Here, we aimed to target the mitochondria of monocyticleukemia (THP-1) radio-resistant cell line cells by a mitochondrial disrupting peptide, D (KLAKLAK)2, and investigate the synergistic effect of Gamma-irradiation and KLA for tumor cells inhibition in vitro. MATERIAL AND METHODS: In this experimental study, KLA was delivered into THP-1 cells using a Cell-Penetrating Peptide (CPP).The cells were then exposed to gamma-ray radiation both in the presence and absence of KLA conjugated with CPP. The impacts of KLA, ionizing radiation or combination of both were then evaluated on the cell proliferation and apoptosis of THP-1 cells using MTT assay and flow cytometry, respectively. RESULTS: The MTT assay indicated the anti-proliferative effects of combined D (KLAKLAK)2 peptide with ionizing radiation on THP-1cells. Moreover, synergetic effects of KLA and ionizing radiation reduced cell viability and consequently enhanced cell apoptosis. CONCLUSION: Using KLA peptide in combination with ionizing irradiation increases the anticancer effects of radio-resistant THP-1 cells. Therefore, the combinational therapy of (KLAKLAK)2 and radiation is a promising strategy for cancer treatment the in future.
ABSTRACT
PURPOSE: MicroRNAs are small single-strand noncoding RNAs that can be deregulated in a variety of cancers. Over the past few years, multiple markers have been discovered in chronic lymphocytic leukemia (CLL). Among these, miRNAs seem to have important roles in the pathogenesis of CLL. The development and validation of miRNA-expression patterns as biomarkers should have a significant impact in cancer diagnosis, therapeutic success, and increasing the life expectancy of patients. In this study, to specify the utility of circulatory miRNA expression as noninvasive and useful biomarkers for CLL, we analyzed the dysregulation of seven miRNAs: miR30d, miR25-3p, miR19a-3p, miR133b, miR451a, miR145, and miR144 in CLL-patient sera. METHODS: Thirty untreated patients with flow-cytometry confirmation of CLL were chosen. Serum samples were collected from 30 newly diagnosed CLL patients. Fifteen healthy samples were taken for comparison as controls. RNA was extracted using Trizol. RNA from CLL patient specimens was compared to controls with real-time PCR. RESULTS: Seven miRNAs were differently expressed between CLL and normal specimens using the comparative 2-ΔΔCt method. miRNAs 133b, 25-3p, 451a, 145, 19a-3p, and 144 were overexpressed in sera obtained from CLL patients, and miRNA-30d was underexpressed in patient samples. Among these seven miRNAs, miR19a-3p and miR25-3p showed the most deregulation in CLL patients. CONCLUSION: Real-time PCR is an applied means to perform high-throughput investigation of serum-RNA samples. We assessed the expression of seven miRNAs in CLL patients by this method. The results demonstrated that the use of miRNA-expression profiling may have an impressive role in the diagnosis of CLL. In addition, miRNA 19a-3p and 25-3p are known oncogenes with therapeutic and potential biomarkers.
